The invention relates to virulence factors and methods for identifying drugs that inhibit pathogen infections.
The gram-positive pathogens in the genus Enterococcus are an increasingly problematic source of nosocomial infections, in part due to multi-drug resistance. Enterococcus can cause diseases such as bacteremia and endocarditis. These pathogens can also infect the urinary tract and skin wounds in immunocompromised individuals. Infection can be fatal if the bacteria cannot be neutralized.
Despite their increasing prevalence as infectious agents, little is known about how these bacteria cause disease. Only cytolysin and aggregation substance have been studied rigorously enough to be established as virulence factors in mammalian models of Enterococcus faecalis pathogenesis. Other virulence factors, such as certain proteases, are believed to contribute to pathogenesis, but have not been studied adequately in mammalian model systems.
One reason that little is known about Enterococcal virulence factors is that the model systems used to study these bacteria, the favorite being a rabbit model of endocarditis, are expensive and unwieldy. Using a mammalian model system to screen for these virulence factors would be virtually impossible. Accordingly, there exists a need for straightforward, inexpensive, and reliable methods to identify Enterococcal virulence factors. Also needed, are easy, accurate screening methods that would greatly simplify the drug discovery process aimed at identifying molecules that inhibit Enterococcal pathogenicity or promote host resistance to this pathogen.